Full-length article Stromal Cell Therapy|Articles in Press

Mesenchymal stromal cells regulate THP-1–differentiated macrophage cytokine production by activating Akt/mammalian target of rapamycin complex 1 pathway

  • Jung Hwa Ko
    Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Jongno-gu, Seoul, Korea
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  • Joo Youn Oh
    Correspondence: Joo Youn Oh, Department of Ophthalmology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea.
    Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Jongno-gu, Seoul, Korea

    Department of Ophthalmology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea
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Published:April 29, 2023DOI:


      Background aims

      The Akt/mammalian target of rapamycin (mTOR) pathway in macrophages converges inflammatory and metabolic signals from multiple receptors to regulate a cell's survival, metabolism and activation. Although mesenchymal stromal cells (MSCs) are well known to modulate macrophage activation, the effects of MSCs on the Akt/mTOR pathway in macrophages have not been elucidated.


      We herein investigated whether MSCs affect the Akt/mTOR complex 1 (mTORC1) pathway to regulate macrophage polarization.


      Results showed that human bone marrow–derived MSCs induced activation of Akt and its downstream mTORC1 signaling in THP-1–differentiated macrophages in a p62/sequestosome 1–independent manner. Inhibition of Akt or mTORC1 attenuated the effects of MSCs on the suppression of tumor necrosis factor-α and interleukin-12 production and the promotion of interleukin-10 and tumor growth factor-β1 in macrophages stimulated by lipopolysaccharide/ATP. Conversely, activation of Akt or mTORC1 reproduced and potentiated MSC effects on macrophage cytokine production. MSCs with cyclooxygenase-2 knockdown, however, failed to activate the Akt/mTORC1 signaling in macrophages and were less effective in the modulation of macrophage cytokine production than control MSCs.


      These data demonstrate that MSCs control THP-1–differentiated macrophage activation at least partly through upregulation of the Akt/mTORC1 signaling in a cyclooxygenase-2–dependent manner.


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